Symbolic sequence learning is associated with cognitive-affective profiles in female FMR1 premutation carriers

C. M. Kraan, D. R. Hocking, J. L. Bradshaw, N. Georgiou-Karistianis, S. A. Metcalfe, A. D. Archibald, J. Fielding, J. Trollor, J. Cohen, K. M. Cornish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers. Analysis of performance on the symbolic serial reaction time task showed that when compared with control participants, females with the PM allele had a comparable number of errors, yet significantly longer mean response latencies at each of the eight task blocks.

Original languageEnglish
Pages (from-to)385-393
Number of pages9
JournalGenes, Brain and Behavior
Issue number4
Publication statusPublished - Apr 2014
Externally publishedYes


  • Cerebellar cognitive affective syndrome
  • Cortico-cerebellar networks
  • FMR1 gene
  • FMRP
  • Phenotype
  • Premutation carrier


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